rs13331

Positions:

• chr17-7190147-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321075.3(DLG4):​c.*561T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 149,298 control chromosomes in the GnomAD database, including 38,526 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.71 (38488 hom., cov: 24)
  • Exomes 𝑓: 0.54 (38 hom.)
• Consequence: DLG4 NM_001321075.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

Genes affected

DLG4 (HGNC:2903): (discs large MAGUK scaffold protein 4) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG4	NM_001321075.3	c.*561T>C		3_prime_UTR_variant	20/20	ENST00000399506.9	NP_001308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000399506.9	c.*561T>C		3_prime_UTR_variant	20/20	2	NM_001321075.3	ENSP00000382425	A1

Frequencies

GnomAD3 genomes AF: 0.711 AC: 105947 AN: 148938 Hom.: 38432 Cov.: 24

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.706

GnomAD4 exome AF: 0.536 AC: 135 AN: 252 Hom.: 38 Cov.: 0 AF XY: 0.567 AC XY: 76 AN XY: 134

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.526

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.700

Gnomad4 NFE exome AF: 0.526

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.712 AC: 106055 AN: 149046 Hom.: 38488 Cov.: 24 AF XY: 0.711 AC XY: 51621 AN XY: 72554

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.710

Alfa AF: 0.672 Hom.: 14472

Bravo AF: 0.708

Asia WGS AF: 0.695 AC: 2417 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.13
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13331; hg19: chr17-7093466;